基于网络药理学和分子对接技术探析缩泉丸治疗膀胱过度活动症的作用机制  

Exploration of the mechanism of Suoquan Wan in the treatment of overactive bladder based on network pharmacology and molecular docking technology

作　　者：付远杰 俞旭君 常德贵[3] 董良[1,2] FU Yuanjie;YU Xujun;CHANG Degui;DONG Liang

机构地区：[1]成都中医药大学,四川成都610075 [2]成都中医药大学附属生殖妇幼医院,四川成都610041 [3]成都中医药大学附属医院,四川成都610075

出　　处：《中医临床研究》2024年第9期54-60,共7页Clinical Journal Of Chinese Medicine

摘　　要：目的:通过网络药理学和分子对接技术探析缩泉丸治疗膀胱过度活动症(Overactive Bladder,OAB)的分子机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获得缩泉丸活性成分,利用Uniprot数据库获取缩泉丸活性成分对应的靶标基因。从OMIM、Gene Cards、Drug Bank数据库中检索得到OAB有关靶点,并取活性成分靶点和OAB相关靶点的交集以得出共同靶点。Cytoscape 3.9.1软件被用来绘制中药-活性成分-靶点网络图以直观显示活性成分与靶点之间的相互作用,并将共同靶点上传到STRING数据库用来挖掘网络中的核心靶点。采用Metascape数据库对共同靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后运用Auto Dock Tools 1.5.7对缩泉丸的核心成分与核心靶点进行分子对接验证。结果:研究发现缩泉丸通过槲皮素、豆甾醇、β-谷甾醇等核心成分,作用于丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase1,AKT1)、白细胞介素(Interleukin,IL)-6、IL-1B、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等核心靶点,调节缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)信号通路、钙信号通路、环磷酸鸟苷(Cyclic Guanosine Monophosphate,c GMP)-蛋白激酶G(Protein Kinase G,PKG)信号通路等,并且参与对氮化合物、有机环化合物、蛋白质磷酸化等生物学过程以治疗OAB。分子对接结果表明缩泉丸中的豆甾醇、β-谷甾醇与AKT1、肿瘤蛋白p53(Tumor Protein p53,TP53)、IL-6、TNF等核心靶点均具有较好的结合活性。结论:本研究通过网络药理学和分子对接技术阐释了缩泉丸调节OAB的潜在成分、靶点及通路,为进一步研究缩泉丸治疗OAB的具体机制提供了方向。Objective:To explore the molecular mechanism of Suoquan Wan(缩泉丸)in treating overactive bladder(OAB)by network pharmacology and molecular docking technology.Methods:The active components of Suoquan Wan and their corresponding target genes were obtained through TCMSP and Uniprot database,respectively.The related targets of OAB were retrieved from the databases of OMIM,GeneCards and DrugBank,and the common targets were obtained by intersecting the drug targets and OAB related targets.Cytoscape 3.9.1 software was used to map the network diagram of traditional Chinese medicine-active components-targets to directly show the interaction between active components and targets.The common targets were uploaded to String database to mine the core targets in the network.Metascape database was used to analyze the common targets for GO functional enrichment and KEGG pathway enrichment.Finally,AutoDockTools 1.5.7 was used to verify the molecular docking between the core components and core targets of Suoquan Wan.Results:It was found that through quercetin,stigmasterol,β-sitosterol and other core components,Suoquan Wan acted on core targets such as AKT1,IL-6,IL-1B and TNF,regulated HIF-1 signal pathway,calcium signal pathway and cGMP-PKG signal pathway,and participated in biological processes such as nitrogen compounds,organic ring compounds and protein phosphorylation to treat OAB.The results of molecular docking showed that stigmasterol andβ-sitosterol in Suoquan Wan had good binding activity with core targets such as AKT1,TP53,IL-6 and TNF.Conclusion:This study explains the potential components,targets and pathways of Suoquan Wan in regulating OAB by network pharmacology and molecular docking technology.It provides a direction for the further study of the specific mechanism of Suoquan Wan in treating overactive bladder.

关 键 词：缩泉丸 膀胱过度活动症 网络药理学 分子对接 

分 类 号：R256.5[医药卫生—中医内科学]